publication of the ESC/ACC recommendations for as- As the ESC/ACC Committee indicated, the new defi-
says to achieve the recommended level of precision. nition has had wide implications for patients and clini-
Any assays that don’t measure up should be with- cal practice. The Committee’s recommendations affect
drawn in the interests of patient care. driving and rehabilitation guidelines; sick leave and
In an article accompanying the paper by Newby et disability entitlements; employers’ perceptions about
al,8 Apple et al9 make further comments about imple- employability; advice as to when patients can return to
mentation of the ESC/ACC recommendations. They work or fly; pilot licensing; life, health and travel insur-
make a number of recommendations, including using a ance; coding of diagnostic groups; epidemiology; clini-
cut-off value of ⱕ10% imprecision (which was above cal trials; and health funding and public policy.
the 99th percentile of the reference range for all as- In New Zealand the new definitions have already
says) until assays improve. This idea has considerable been accepted by the Land Transport Safety Authority,
merit. They also make recommendations regarding the which governs driver licencing. Thus patients who
definition of MI associated with PCI, namely that an have a positive troponin test (without elevation of
increase above the cut-off value determined at 10% other myocardial proteins) after PCI or in connection
imprecision should be considered an MI, and that an with a non-ST-elevation acute coronary syndrome are
increase of ⱖ25% in cases where the troponin level classified in the same way and must not drive a private
was already increased should be defined as recurrent vehicle for 2 weeks, and must not drive a commercial
injury associated with PCI. vehicle for 4 weeks.
There are now several troponin assays available (eg, The psychological impact of the diagnosis of MI on
the Roche Diagnostics troponin T assay) that fulfil the individuals and their families should not be underesti-
ESC/ACC recommendations (personal communication). mated, and the response—whether conscious or sub-
Several troponin I assays come close to fulfilling the conscious—will vary enormously. Of course, telling
patients that they have had a heart attack should not
recommendations. Apart from the precision of the as-
be the only information given. Not all MIs are the
says themselves, it will be important for individual lab-
same,14 and the implications for social activities, em-
oratories to show that they can achieve the required
ployment, and patients’ prognoses will vary widely
standards routinely.10
according to the extent of myocardial necrosis, evi-
Another issue is that some laboratories may assay
dence of inducible ischemia, predisposition to ventric-
troponins only once a day or just several times a week.
ular arrhythmias, the severity of coronary artery dis-
The ACC/American Heart Association (AHA) guidelines
ease, whether revascularization has been performed,
recommend that laboratories should provide cardiac
and the degree of impairment of left ventricular func-
biomarker results within 30 to 60 minutes,11 and the
tion. This information should be conveyed and dis-
US National Academy of Clinical Biochemistry recom-
cussed with patients and their families.
mends bedside or point-of-care testing if laboratories Fourth, the ESC/ACC Committee gave no recommen-
cannot provide cardiac biomarker results consistently dations as to the definition of MI in patients undergo-
within 1 hour.12 ing CABG, although a consensus conference in 1998
Third, the ESC/ACC Committee did not give any rec- recommended that the CK-MB threshold should be 5
ommendations for an implementation strategy. Many times the upper limit of normal.15 (The same confer-
hospitals worldwide still do not perform troponin test- ence recommended that the CK-MB threshold for PCI
ing. For example, in a recent survey, only 70% of hos- should be 3 times the upper limit of normal). Defining
pitals in Scotland had troponin testing available.13 Hap- the troponin levels that correlate with increased risk
hazard introduction of the new definition has already after CABG is a different concept than defining the
led to hospitals in the same community using different level at which to label an event “MI” based on an isch-
criteria for the diagnosis of MI. The transition might emic cause. In the setting of CABG, a positive tropo-
have been smoother if the introduction of the new nin test signifies that myocyte necrosis has occurred,
definitions had been coordinated by national cardiac and patients should be risk-stratified according to their
societies, the World Heart Federation and the World troponin level and other risk factors. There is clear
Health Organization. Major educational efforts are re- evidence that patients with increased cardiac protein
quired to educate doctors and the public that there is levels after CABG have worse outcomes. In the Arterial
now a new definition of what constitutes a heart at- Revascularization Therapy (ARTS) Study,16 which com-
tack, and national heart foundations should take a lead- pared multivessel stenting with CABG, elevated CK-MB
ing role in such initiatives. Many patients will now be levels were detected in 30.5% of patients treated with
told that they have had a heart attack who would not PCI and 62% of those treated with CABG. The 12-
have been diagnosed as such previously. It is impor- month mortality rate in the latter group increased sig-
tant that they are told that for most patients the future nificantly when CK-MB levels rose above 5 times nor-
after a heart attack is excellent. mal (7% vs 0% in the 38% of patients without elevated
American Heart Journal
White 935
Volume 144, Number 6
Figure 1
Microvascular obstruction after plaque rupture. Despite recurrent micro emboli, the levels of CK-MB do not reach the diagnostic threshold,
whereas because of the long half life and higher sensitivity of the assays, the diagnostic threshold for troponin is reached. CK-MB, Creatine
kinase-MB. Adapted with permission from: Goldman BU, Christenson RH, Hamm CW, et al. Implications of troponin testing in clinical medi-
cine. Curr Control Trials Cardiovasc Med 2001;2:75-84.
fissured and unstable plaque in the left anterior de- cardial protection, and factors related to graft patency,
scending coronary artery is likely to have an unstable including plaque and platelet embolism, spasm and
clinical course and a poor prognosis even though the thrombosis.
rise in troponin levels may be no greater. Where the resources are available, troponin testing
The prognostic importance of troponin elevations should be considered mandatory for prognostic evalua-
after PCI was shown in the Sibrafiban versus aspirin to tion of patients with non-ST-elevation acute coronary
Yield Maximum Protection from ischemic Heart events syndromes, diagnosis of MI, and treatment selection
post-acute corONary sYndromes (SYMPHONY) trial, in (also taking into account other clinical information and
which 82% of patients underwent PCI with stenting. tests).23-26 Use of the new definitions of MI may actu-
Forty-eight percent had elevated troponin I levels, ally reduce costs because the greater precision of tro-
whereas only 29% had elevated CK-MB levels.18 Twen- ponin testing for risk assessment should mean that un-
ty-six percent of patients who tested negative for tro- necessary hospitalization and drug usage can be
ponins before the procedure tested positive after the reduced in low-risk patients, while those with elevated
procedure, and these patients had a combined hazard troponin levels should be more likely to receive appro-
ratio (HR) for death or MI within 90 days of 4.3 (95% priate antithrombotic therapy, revascularization,27,28
CI 1.4-13.5) versus those without elevated troponin and secondary preventative measures such as aspirin
levels. Multivariate analysis including baseline charac- and statins.
teristics and procedural variables showed that troponin A heart attack in 2002 is not the same as a heart at-
I (entered as a continuous variable) was an indepen- tack in previous years. I believe that the new defini-
dent predictor of the time to death or MI (P ⫽ .0001). tion will lead to improved patient care and conse-
In a recent meta-analysis of 2605 patients who were quently better patient outcomes. There is much work
followed up for 1.5 to 77 months after PCI, those with to be done to ensure that assays are of an appropriate
elevated troponin levels (measured using a variety of standard and to educate the public that, as the old Ted
troponin assays and a variety of cutpoints) after the Parsons song says, “Things ain’t what they used to be.”
procedure were found to have double the rates of
mortality (HR 2.09, CI 1.42-3.08) and MI (HR 2.27, CI
1.62-3.16).19 Troponin elevations occur more fre- References
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